کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2796505 1155605 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Expression and cellular distribution of TLR4, MyD88, and NF-κB in diabetic renal tubulointerstitial fibrosis, in vitro and in vivo
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Expression and cellular distribution of TLR4, MyD88, and NF-κB in diabetic renal tubulointerstitial fibrosis, in vitro and in vivo
چکیده انگلیسی

AimInflammation and extracellular matrix hyperplasia are crucial in the pathogenesis of tubulointerstitial fibrosis (TIF) involved in diabetic nephropathy (DN). Macrophage accumulation plays a major role, but whether immune factors contribute to DN pathogenesis is not well understood. This study aimed to investigate TLR4-MyD88-NF-κB-dependent pathway's involvement in TIF pathogenesis.MethodsSTZ-induced diabetic rats and rat renal tubular epithelial NRK-52E cells cultured under high glucose conditions were used as in vivo and in vitro models, respectively. Real-time RT-PCR, western blot, immunohistochemistry and immunofluorescence were performed to examine the mRNA and protein levels of TLR4, MyD88, NF-κB, MCP-1, and α-SMA.ResultsCompared with 5.5 mmol/L glucose, treatment of NRK-52E cells with 25 and 50 mmol/L d-glucose resulted in significantly increased TLR4 and MyD88 mRNA and protein levels (P < 0.05). TLR4 and MyD88 were detected in the cytoplasm of most NRK-52E cells cultured under high glucose. Pronounced damage in the renal tubulointerstitium was observed in diabetic rats (scores: 3.82 ± 0.65 vs. 0.38 ± 0.08, P < 0.01). Compared with the normal controls, a sharp upregulation of TLR4, MyD88, NF-κB p65, MCP-1, and α-SMA mRNA and protein levels was observed in diabetic rat kidneys (P < 0.05). In diabetic animals, TLR4 and MyD88 were strongly expressed in the cytoplasm, while NF-κB p65 was widely expressed in cytoplasm and nuclei of renal tubular epithelial cells.ConclusionThe inflammatory reaction and epithelial-mesenchymal transformation observed in renal tubulointerstitium may be the result of overactivation of the TLR4-MyD88-NF-κB-dependent innate immunity under high glucose, and may be involved in DN occurrence and progression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Diabetes Research and Clinical Practice - Volume 105, Issue 2, August 2014, Pages 206–216
نویسندگان
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